{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:35:18Z","timestamp":1792082118254,"version":"4.4.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Cardiovascular Quality and Outcomes"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Although cholesterol-lowering medications can reduce the risk of recurrent cardiovascular events, premature discontinuation limits effectiveness. Discontinuation rates have not been systematically reported for lipid-lowering trials.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results:<\/jats:title>\n            <jats:p>\n              We evaluated medication discontinuation in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial), which evaluated placebo+simvastatin versus ezetimibe+simvastatin in patients hospitalized with the acute coronary syndrome and followed longitudinally postdischarge. Reasons for discontinuation were evaluated from randomization through study end (median 71.9 [interquartile range 51.8\u201385.8] months). Kaplan-Meier (KM) discontinuation rates were evaluated at 30 days, 1 year, and through year 7, and compared by treatment arm and region, with Cox proportional hazards modeling used to evaluate predictors of discontinuation. Overall, 46.7% of subjects discontinued study medication (KM rate by study end 50.9% [95% CI, 50.1%\u201351.7%]). The risk of discontinuation was highest early in the trial but decreased with increasing time, with a terminal KM rate per 100 person-years of 8.4 (8.2\u20138.6) from years 1 to 7. Discontinuation was higher in the placebo+simvastatin versus ezetimibe+simvastatin arm (KM rate 52.0% versus 49.8%,\n              <jats:italic>P<\/jats:italic>\n              =0.049) and was highest in the United States (7-year KM rate 57.4%). In multivariable modeling, smoking, prior revascularization, hypertension, unstable angina, female sex, nonwhite race, and US location were associated with higher discontinuation rates.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Although discontinuation was highest early and stabilized to 8% per year, because of prolonged follow-up, most discontinuation occurred after year 1. Adding ezetimibe to statin therapy did not increase discontinuation risk. Geographic differences and patient-level factors should be considered in trial design and analysis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Trial Registration:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              . Unique identifier: NCT00202878.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circoutcomes.118.005041","type":"journal-article","created":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T10:00:31Z","timestamp":1547200831000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":33,"title":["Medication Discontinuation in the IMPROVE-IT Trial"],"prefix":"10.1161","volume":"12","author":[{"given":"Ann Marie","family":"Navar","sequence":"first","affiliation":[{"name":"Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., M.T.R., J.A.W., Y.L., L.K.N., M.A.B.)."},{"name":"Duke Forge, Duke University, Durham, NC (A.M.N., R.M.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew T.","family":"Roe","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., M.T.R., J.A.W., Y.L., L.K.N., M.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"White","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., M.T.R., J.A.W., Y.L., L.K.N., M.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher P.","family":"Cannon","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Boston, MA (C.P.C., R.P.G., E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliya","family":"Lokhnygina","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., M.T.R., J.A.W., Y.L., L.K.N., M.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Kristin","family":"Newby","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., M.T.R., J.A.W., Y.L., L.K.N., M.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Giugliano","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., M.T.R., J.A.W., Y.L., L.K.N., M.A.B.)."},{"name":"TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Boston, MA (C.P.C., R.P.G., E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Tershakovec","sequence":"additional","affiliation":[{"name":"Merck &amp; Co, Inc, Rahway, NJ (A.M.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Braunwald","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Boston, MA (C.P.C., R.P.G., E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Califf","sequence":"additional","affiliation":[{"name":"Duke Forge, Duke University, Durham, NC (A.M.N., R.M.C.)."},{"name":"Department of Medicine, Stanford University, CA (R.M.C.)."},{"name":"Verily Life Sciences, South San Francisco, CA (R.M.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Blazing","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., M.T.R., J.A.W., Y.L., L.K.N., M.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61350-5"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1410489"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.04.102"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.002658"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.166.17.1842"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-016-0283-6"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2015.03.019"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i3305"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.7326\/M18-0543"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1497.2004.30516.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2012.04.012"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2013.03.001"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv641"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2010.03.004"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0907569"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0800742"},{"key":"e_1_3_3_18_2","unstructured":"European Society of Cardiology. 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